长链非编码RNA在肿瘤发生及发展中的作用机制

长链非编码RNA(lncRNA)是一类转录本长度＞200个核苷酸的非编码RNA(ncRNA),其在肿瘤的发生、发展中发挥重要作用.IncRNA具有多种生物学功能,可以通过诱饵分子、支架分子和向导分子等形式,在表观遗传学水平、转录水平及转录后水平,调控蛋白质编码基因的表达.lncRNA与肿瘤细胞生长和凋亡、侵袭和转移等生物学行为密切相关.进一步阐明IncRNA在肿瘤发生、发展过程中的作用机制,有望为研究者开发肿瘤诊断和治疗的新方法提供思路.笔者拟就lncRNA调控基因表达的作用机制,及其在肿瘤诊断及治疗中的作用进行综述.     

Uncovering the role of genomic "dark matter" in human disease

The human genome encodes thousands of long noncoding RNAs (lncRNAs). Although most remain functionally uncharacterized biological "dark matter," lncRNAs have garnered considerable attention for their diverse roles in human biology, including developmental programs and tumor suppressor gene networks. As the number of lncRNAs associated with human disease grows, ongoing research efforts are focusing on their regulatory mechanisms. New technologies that enable enumeration of lncRNA interaction partners and determination of lncRNA structure are well positioned to drive deeper understanding of their functions and involvement in pathogenesis. In turn, lncRNAs may become targets for therapeutic intervention or new tools for biotechnology.     

Long non-coding (lnc)RNA profiling and the role of a key regulator lnc-PNRC2-1 in the transforming growth factor-β1-induced epithelial–mesenchymal transition of CNE1 nasopharyngeal carcinoma cells

ObjectivesTo identify key long non-coding (lnc)RNAs responsible for the epithelial–mesenchymal transition (EMT) of CNE1 nasopharyngeal carcinoma cells and to investigate possible regulatory mechanisms in EMT.MethodsCNE1 cells were divided into transforming growth factor (TGF)-β1-induced EMT and control groups. The mRNA and protein expression of EMT markers was determined by real-time quantitative PCR and western blotting. Differentially expressed genes (DEGs) between the two groups were identified by RNA sequencing analysis, and DEG functions were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. EMT marker expression was re-evaluated by western blotting after knockdown of a selected lncRNA.ResultsTGF-β1-induced EMT was characterized by decreased E-cadherin and increased vimentin, N-cadherin, and Twist expression at both mRNA and protein levels. Sixty lncRNA genes were clustered in a heatmap, and mRNA expression of 14 dysregulated lncRNAs was consistent with RNA sequencing. Knockdown of lnc-PNRC2-1 increased expression of its antisense gene MYOM3 and reduced expression of EMT markers, resembling treatment with the TGF-β1 receptor inhibitor LY2109761.ConclusionVarious lncRNAs participated indirectly in the TGF-β1-induced EMT of CNE1 cells. Lnc-PNRC2-1 may be a key regulator of this and is a potential target to alleviate CNE1 cell EMT.     

非编码RNA在多发性骨髓瘤中的研究进展

研究发现,非编码RNA(non-coding RNAs,ncRNA)在多发性骨髓瘤(multiple myeloma,MM)的发生发展以及治疗中起到了重要作用。例如:某些微小RNA(microRNA,miRNA)可以调控基因表达,影响细胞自噬、凋亡等生理病理进程及蛋白质合成等,从而为MM诊断、治疗及预后评估提供依据。长链非编码RNA(long noncoding RNA,lncRNA)可以参与细胞分化,结合转录因子修饰组蛋白,特异性调控基因组等,为MM患者提供潜在的治疗靶点。而环状RNA(circular RNA,circRNA)拥有转录后调节功能,可以调节基因表达,从而抑制MM的细胞活性及细胞增殖,进一步诱导细胞凋亡。本文就不同非编码RNA的功能特征以及其在多发性骨髓瘤中的研究进展作一综述。     

长链非编码RNA与肿瘤诊断

非编码RNA参与了多种疾病尤其是肿瘤发生发展的调控过程,是近期研究热点之一。随着高通量筛选方法的完善,越来越多的lncRNA分子被发现,并有望成为新型肿瘤诊断标志物和肿瘤治疗的靶点。近期研究提示IncRNA在肿瘤诊断和治疗方面具有良好的临床应用前景。本文介绍了lncRNA近期研究进展,相关lncRNA数据库的使用,并着重介绍了lncRNA与肿瘤诊断和预后关系研究情况。     

Integrated analysis of lncRNA–mRNA networks associated with an SLA titanium surface reveals the potential role of HIF1A-AS1 in bone remodeling

Microstructured titanium surface implants, such as typical sandblasted and acid-etched (SLA) titanium implants, are widely used to promote bone apposition in prosthetic treatment by dental implants following tooth loss. Although there are multiple factors associated with the superior osseointegration of an SLA titanium surface, the molecular mechanisms of long noncoding RNAs (lncRNAs) are still unclear. In this study, we characterized smooth (SMO) and SLA surfaces, and compared the osteoinduction of these surfaces using human bone marrow-derived mesenchymal stem cells (hBMSCs) in vitro and implants in a rat model in vivo. Then, we used microarrays and bioinformatics analysis to investigate the differential expression profiles of mRNAs and lncRNAs on SMO and SLA titanium surfaces. An lncRNA–mRNA network was constructed, which showed an interaction between lncRNA HIF1A antisense RNA 1 (HIF1A-AS1) and vascular endothelial growth factor. We further found that knockdown of HIF1A-AS1 significantly decreased osteogenic differentiation of hBMSCs. This study screened SLA-induced lncRNAs using a systemic strategy and showed that lncRNA HIF1A-AS1 plays a role in promotion of new bone formation in the peri-implant area, providing a novel insight for future surface modifications of implants.

Long non-coding RNA HIF1A-AS1 plays a role in SLA titanium surface-induced osteogenic differentiation of hBMSCs by regulating p38 MAPK.     

长链非编码RNA在消化系统肿瘤中的研究进展

长链非编码RNA（lncRNA）是一系列广泛转录自人及其他哺乳动物基因组的长度超过200 nt的核苷酸片段,通常没有蛋白编码功能,一度被认为是基因组的转录“噪音”。近年来一些 lncRNA 被发现具有多种生物学功能,成为分子生物学领域研究的热点。已经在多种肿瘤中发现有lncRNA的异常表达,并且异常表达的 lncRNA 和肿瘤的复发、转移及预后有关。本文中将探讨近期发现的与消化系统肿瘤相关的lncRNA,部分着重于具有促癌作用的lncRNA,以期为消化系统肿瘤的诊断、预后及分子治疗提供线索。     

lnc94638 is a testis-specific long non-coding RNA involved in spermatozoa formation in Zeugodacus cucurbitae (Coquillett)

Long non-coding RNAs (lncRNAs) generally display tissue-specific distributions, and testis-specific lncRNAs form the highest proportion of lncRNAs in many species. Here, we presented a detailed analysis of testis-specific lncRNAs in the melon fly, Zeugodacus cucurbitae, a highly destructive insect pest of cucurbitaceous and other related crops. Most testis-specific lncRNAs were found to be long intergenic non-coding RNAs (lincRNA). The size distribution of these lncRNAs ranged between 600 and 1000 nucleotides. Testis-specific lncRNAs that harboured one isoform number and two exons were the most abundant. Compared to other male tissues, the testis had more highly expressed lncRNAs. The quantitative real-time polymerase chain reaction results of 10 randomly selected testis-specific lncRNAs showed expression patterns consistent with RNA-seq data. Further analysis of the most highly expressed testis-specific lncRNA, lnc94638, was undertaken. Fluorescent in situ hybridization assays localized lnc94638 to the apical region of the testis that contains mature spermatozoa. RNA interference-mediated knockdown of lnc94638 expression reduced spermatozoa numbers and impaired the fertility of Z. cucurbitae male. This study provides a catalogue of testis-specific lncRNAs, shows that the testis-specific lnc94638 is involved in spermatogenesis and has the potential to be used for treating male sterility.